Neurometabolic Differences in Psychosis Observed with 7 T Magnetic Resonance Spectroscopy

Altered brain chemistry is thought to contribute to impaired cognition and perceptual functioning in people with psychotic psychopathology (PwPP). As heritable genetic factors shape the development of psychosis, alterations in brain chemistry may extend to biological relatives of PwPP. Magnetic resonance spectroscopy (MRS) is a non-invasive method for quantifying concentrations of various neurochemicals in the human brain. Previous studies using MRS have generally focused on specific diagnoses (eg, schizophrenia), rather than PwPP trans-diagnostically, and comparably few studies have examined relatives. The goal of the current study was to assess neurometabolic differences in PwPP and relatives using MRS in a large number of participants.

As part of the Psychosis Human Connectome Project, we acquired ultra-short echo time (8 ms) MRS data at 7 tesla in both occipital and prefrontal cortices from 64 PwPP, 42 first-degree biological relatives, and 43 controls.

We observed lower levels of N-acetyl-aspartate (NAA) in the occipital lobe in PwPP and relatives versus controls, and a trend toward lower N-acetyl-aspartylglutamate in prefrontal cortex in PwPP versus controls. Lower OCC NAA levels were also evident in diagnostic subgroups of PwPP (schizophrenia and bipolar disorder) compared to controls. We also observed higher levels of glucose in both occipital and prefrontal cortices in PwPP. Hierarchical clustering analyses showed that higher glucose levels were linked to higher psychiatric symptoms, poorer cognition, and impaired visual task performance.

Together, our findings point to alterations in neural metabolism across multiple brain areas in PwPP that are associated with impaired cognitive and perceptual functioning.